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Housing in Environmental Complexity Following Wheel Running Augments Survival of Newly Generated Hippocampal Neurons in a Rat Model of Binge Alcohol Exposure During the Third Trimester Equivalent
Author(s) -
Hamilton Gillian F.,
Boschen Karen E.,
Goodlett Charles R.,
Greenough William T.,
Klintsova Anna Y.
Publication year - 2012
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2011.01726.x
Subject(s) - neun , dentate gyrus , hippocampal formation , bromodeoxyuridine , neurogenesis , hippocampus , endocrinology , environmental enrichment , binge drinking , medicine , stimulation , immunohistochemistry , alcohol , biology , andrology , chemistry , neuroscience , alcohol consumption , biochemistry
Background Binge‐like alcohol exposure in neonatal rats during the brain growth spurt causes deficits in adult neurogenesis in the hippocampal dentate gyrus ( DG ). Previous data from our laboratory demonstrated that 12 days of voluntary wheel running ( WR ) beginning on postnatal day ( PD ) 30 significantly increased the number of newly generated cells evident in the DG on PD 42 in both alcohol‐exposed ( AE ) and control rats, but 30 days later a sustained beneficial effect of WR was evident only in control rats. This study tested the hypothesis that housing rats in environmental complexity ( EC ) following WR would promote the survival of the newly generated cells stimulated by WR , particularly in AE rats. Methods On PD 4 to 9, pups were intubated with alcohol in a binge‐like manner (5.25 g/kg/d), sham‐intubated ( SI ), or reared normally. In Experiment 1, animals were either assigned to WR during PD 30 to 42 or socially housed ( SH ). On PD 42, animals were injected with bromodeoxyuridine ( BrdU ; 200 mg/kg) and perfused 2 hours later to confirm the WR ‐induced stimulation of proliferation. In E xperiment 2, all animals received WR on PD 30 to 42 and were injected with BrdU on the last full day of WR . On PD 42, animals were randomly assigned either to EC ( WR / EC ) or to SH ( WR / SH ) for 30 days and subsequently perfused and brains were processed for immunohistochemical staining to identify BrdU +‐, Ki 67+‐, and BrdU +/ NeuN +‐labeled cells in DG . Results In Experiment 1, WR exposure significantly increased the number of proliferating cells in all 3 postnatal conditions. In Experiment 2, the AE rats given WR / SH had significantly fewer BrdU + cells compared with control rats given WR / SH . However, WR / EC experience significantly increased the number of surviving BrdU + cells in both the AE and SI groups compared with WR / SH rats of the same neonatal treatment. Approximately 80% of the surviving BrdU + cells in the DG across the conditions were colabeled with NeuN . Conclusions WR followed by EC could provide a behavioral model for developing interventions in humans to ameliorate hippocampal‐dependent impairments associated with fetal alcohol spectrum disorders.